Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/80018 |
Resumo: | Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η5-C5H4R)(PPh3)(4,4'-R'-2,2'-bipyridine)][CF3SO3], where R = CH3, CHO or CH2OH and R' = H, CH3, CH2OH, or dibiotin ester. The complexes (Ru 1-7) displayed high bioactivity, as shown by low IC50 concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5-7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment. |
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Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugsruthenium complexesanti-colorectal cancer drugsapoptosiscell cycle arrestcytoskeletonCiências Médicas::Medicina BásicaCiências Médicas::Biotecnologia MédicaScience & TechnologyColorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η5-C5H4R)(PPh3)(4,4'-R'-2,2'-bipyridine)][CF3SO3], where R = CH3, CHO or CH2OH and R' = H, CH3, CH2OH, or dibiotin ester. The complexes (Ru 1-7) displayed high bioactivity, as shown by low IC50 concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5-7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment.Fundação para a Ciência e Tecnologia (FCT), I.P./MCTES through national funds (PIDDAC)—UIDB/00100/2020, UIDB/04050/2020 and through PTDC/QUI-QIN/28662/2017. A.V. acknowledges the CEECIND 2017 Initiative (CEECCIND/01974/2017). A.R.B. and R.G.T. thank FCT for their Ph.D. Grants (SFRH/BD/139271/2018 and SFRH/BD/135830/2018, respectively)Multidisciplinary Digital Publishing InstituteUniversidade do MinhoTeixeira-Guedes, CatarinaBrás, Ana RitaTeixeira, Ricardo G.Valente, AndreiaPreto, Ana2022-06-172022-06-17T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/80018engTeixeira-Guedes, C.; Brás, A.R.; Teixeira, R.G.; Valente, A.; Preto, A. Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs. Pharmaceutics 2022, 14, 1293. https://doi.org/10.3390/pharmaceutics140612931999-492310.3390/pharmaceutics14061293https://www.mdpi.com/1999-4923/14/6/1293info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:51:23Zoai:repositorium.sdum.uminho.pt:1822/80018Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:50:15.880459Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs |
title |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs |
spellingShingle |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs Teixeira-Guedes, Catarina ruthenium complexes anti-colorectal cancer drugs apoptosis cell cycle arrest cytoskeleton Ciências Médicas::Medicina Básica Ciências Médicas::Biotecnologia Médica Science & Technology |
title_short |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs |
title_full |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs |
title_fullStr |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs |
title_full_unstemmed |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs |
title_sort |
Ruthenium(II)–cyclopentadienyl-derived complexes as new emerging anti-colorectal cancer drugs |
author |
Teixeira-Guedes, Catarina |
author_facet |
Teixeira-Guedes, Catarina Brás, Ana Rita Teixeira, Ricardo G. Valente, Andreia Preto, Ana |
author_role |
author |
author2 |
Brás, Ana Rita Teixeira, Ricardo G. Valente, Andreia Preto, Ana |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Teixeira-Guedes, Catarina Brás, Ana Rita Teixeira, Ricardo G. Valente, Andreia Preto, Ana |
dc.subject.por.fl_str_mv |
ruthenium complexes anti-colorectal cancer drugs apoptosis cell cycle arrest cytoskeleton Ciências Médicas::Medicina Básica Ciências Médicas::Biotecnologia Médica Science & Technology |
topic |
ruthenium complexes anti-colorectal cancer drugs apoptosis cell cycle arrest cytoskeleton Ciências Médicas::Medicina Básica Ciências Médicas::Biotecnologia Médica Science & Technology |
description |
Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η5-C5H4R)(PPh3)(4,4'-R'-2,2'-bipyridine)][CF3SO3], where R = CH3, CHO or CH2OH and R' = H, CH3, CH2OH, or dibiotin ester. The complexes (Ru 1-7) displayed high bioactivity, as shown by low IC50 concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5-7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-06-17 2022-06-17T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/1822/80018 |
url |
https://hdl.handle.net/1822/80018 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Teixeira-Guedes, C.; Brás, A.R.; Teixeira, R.G.; Valente, A.; Preto, A. Ruthenium(II)–Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs. Pharmaceutics 2022, 14, 1293. https://doi.org/10.3390/pharmaceutics14061293 1999-4923 10.3390/pharmaceutics14061293 https://www.mdpi.com/1999-4923/14/6/1293 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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